Iron deficiency is not merely a cause of “anaemia”; it is also an important biomarker that may reflect dysfunction across multiple body systems—particularly when it occurs in adults or without an obvious cause.
What is Iron Deficiency?
Iron deficiency is a condition in which the body lacks sufficient iron to produce haemoglobin in red blood cells. If severe, it progresses to Iron Deficiency Anaemia (IDA).
Cause of Iron deficiency
1. Chronic Blood Loss
This is the most common cause, especially in adults.
- Gastrointestinal (GI) bleeding, such as:
- Peptic ulcer
- Inflammatory bowel disease (IBD)
- Colorectal cancer
- Heavy menstrual bleeding (menorrhagia)
- Use of medications such as NSAIDs, which can irritate the gastric lining
Clinical insight:
Iron deficiency may be an early warning sign of gastrointestinal malignancy, particularly in men and postmenopausal women.
2. Chronic Inflammation (Inflammaging)
Low-grade chronic inflammation stimulates the production of hepcidin, which inhibits iron absorption and utilisation.
Seen in conditions such as:
- Metabolic syndrome
- Obesity
- Chronic infections
- Autoimmune diseases (e.g. SLE, RA)
Clinical insight:
Ferritin levels may be “elevated”, yet the body remains functionally iron deficient.
3. Malabsorption Syndromes
When the body cannot effectively absorb iron:
- Coeliac disease
- Helicobacter pylori infection
- Post-bariatric surgery
- Chronic gastritis or low stomach acid
Clinical insight:
Should be suspected when iron supplementation does not lead to improvement.
4. Hormonal Imbalance
Particularly involving endocrine systems linked to metabolism:
- Hypothyroidism (reduced thyroid hormone production), leading to slower metabolism and reduced red blood cell (RBC) production
- Oestrogen imbalance, affecting menstrual cycles and blood loss
- Adrenal dysfunction / cortisol dysregulation
Clinical insight:
Iron deficiency and thyroid dysfunction are frequently seen together.
5. Nutritional Deficiency
Inadequate dietary intake of iron (e.g. unplanned vegetarian or vegan diets), or deficiency of key cofactors such as:
- Vitamin C (enhances iron absorption)
- Vitamin B12 and folate (essential for red blood cell production)
Clinical insight:
Assessment should include a full micronutrient panel.
6. Increased Demand / Recovery States
- Endurance athletes
- Pregnancy
- Recovery after surgery or illness
Clinical insight:
In these groups, iron deficiency may reflect an imbalance rather than disease.
7. Chronic Disease and Metabolic Links
Iron deficiency is associated with:
- Chronic kidney disease
- Heart failure
- Cognitive decline
- Fatigue and mitochondrial dysfunction
Longevity insight:
Iron plays a crucial role in mitochondrial function and cellular energy production.
What Happens in the Body?
1. Early Stage (Iron Depletion)
- Low ferritin (reduced iron stores)
- No anaemia yet
- Often asymptomatic
2. Intermediate Stage (Iron-Deficient Erythropoiesis)
- Impaired red blood cell production
- Red blood cells become smaller (microcytic)
- Reduced MCV
3. Established Stage (Iron Deficiency Anaemia)
- Low haemoglobin (Hb)
- Small, pale red blood cells (microcytic, hypochromic)
- Fatigue, palpitations, dizziness
Common Causes
- Chronic blood loss (e.g. heavy menstruation, GI bleeding)
- Inadequate dietary intake
- Malabsorption (e.g. intestinal inflammation)
- Pregnancy
Common Symptoms
- Fatigue and weakness
- Pale skin and conjunctiva
- Palpitations and shortness of breath
- Hair loss, brittle nails
- Pica (craving non-food items such as ice, soil, paper, or powders)
Key Laboratory Markers
- Ferritin (first marker to decline)
- Serum iron
- TIBC
- Transferrin saturation
- Haemoglobin and MCV (in later stages)
Note: Ferritin is the most important early marker, but it is also an acute-phase reactant and may be elevated during inflammation.
Laboratory Evaluation Panel for Iron Deficiency
An Iron Deficiency Evaluation Panel may include:
- CBC
- Ferritin
- Serum iron / TIBC / Transferrin saturation
- Transferrin level
- hs-CRP (inflammation marker)
- Vitamin B12 / Folate (serum)
- Thyroid panel (TSH, FT3, FT4)
- Stool FIT test (if GI bleeding is suspected)
Dr Apakorn Polthian
References
- Camaschella, C. (2015). Iron-deficiency anemia. New England Journal of Medicine, 372(19), 1832–1843.
- Cappellini, M. D., Musallam, K. M., & Taher, A. T. (2020). Iron deficiency anaemia revisited. Journal of Internal Medicine, 287(2), 153–170.
- DeLoughery, T. G. (2017). Iron deficiency anemia. Medical Clinics of North America, 101(2), 319–332.
- Gastrointestinal Society. (2017). Iron deficiency anemia and gastrointestinal disorders. Canadian Journal of Gastroenterology & Hepatology, 2017, 1–6.
- Killip, S., Bennett, J. M., & Chambers, M. D. (2007). Iron deficiency anemia. American Family Physician, 75(5), 671–678.
- Means, R. T. Jr. (2020). Iron deficiency and iron deficiency anemia: Implications and impact in pregnancy, fetal development, and early childhood parameters. Nutrients, 12(2), 447.
- Short, M. W., & Domagalski, J. E. (2013). Iron deficiency anemia: Evaluation and management. American Family Physician, 87(2), 98–104.
- World Health Organization. (2020). WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations.
